Instability and/or presence of undesirable species in an antibody formulation may pose problems including simple inconvenience, such as the need to store or handle the formulation in a particular way, and safety and efficacy concerns, such as those caused by increased toxicity or immunogenicity. One characteristic that is observed with some antibodies is the tendency for the antibody molecules to self-associate reversibly, also known as reversible self-association (RSA). RSA of antibodies in a given formulation may be influenced by antibody concentration, temperature and/or pH. The RSA tendency of an antibody in a formulation can have a significant impact on the physical properties of the antibody formulation, potentially affecting long-term stability, manufacturability, user compliance, and potential product safety and efficacy. For example, the RSA tendency of antibodies in some antibody formulations is significant when maintained at or below storage temperatures of about 2° C.-8° C. Although this RSA tendency may completely or substantially be resolved following extended incubation at room temperature (e.g., greater than one hour), the need for such extended incubation may negatively impact the efficient and consistent use of the formulation.
There is a need for methods to facilitate the identification of suitable formulation conditions to maximize stability and minimize RSA tendency. For example, there is a need for methods and formulations that will allow therapeutic antibodies to be stable with minimal RSA while stored at a wide range of conditions (e.g., temperature, antibody concentration and pH).